Naphthyl compounds, intermediates, compositions, and methods

Abstract

The present invention is related to methods for treating pathological conditions resulting from an estrogen deficiency, such as cardiovascular disease and osteoporosis, and is further related to methods for treating estrogen-dependent cancer, such as breast and uterine cancer, employing compounds of formula I

I claim:  
     
       1. A method for treating pathological conditions resulting from an estrogen deficiency comprising administering to a women in need of treatment an effective amount of a compound of formula I                    
       wherein 
       R 1  is —H, —OH, —O(C 1 -C 4  alkyl), —OCOC 6 H 5 , —OCO(C 1 -C 6  alkyl), or —OSO 2 (C 2 -C 6  alkyl);  
       R 2  is —H, —OH, —O(C 1 -C 4  alkyl), —OCOC 6 H 5 , —OCO(C 1 -C 6  alkyl), —OSO 2 (C 2 -C 6  alkyl), or halo;  
       R 3  is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; and  
       n is 2 or 3; and  
       or a pharmaceutically acceptable salt thereof. 
     
     
       2. A method according to claim  1  wherein the pathological condition is osteoporosis. 
     
     
       3. A method according to claim  1  wherein the pathological condition is related to a cardiovascular disease. 
     
     
       4. A method according to claim  3  wherein the cardiovascular disease is hyperlipidemia. 
     
     
       5. A method for treating estrogen-dependent cancer comprising administering to a woman in need of treatment an effective amount of a compound of formula I                    
       wherein 
       R 1  is —H, —OH, —O(C 1 -C 4  alkyl), —OCOC 6 H 5 , —OCO(C 1 -C 6  alkyl), or —OSO 2 (C 2 -C 6  alkyl);  
       R 2  is —H, —OH, —O(C 1 -C 4  alkyl), —OCOC 6 H 5 , —OCO(C 1 -C 6  alkyl), —OSO 2 (C 2 -C 6  alkyl), or halo;  
       R 3  is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; and  
       n is 2 or 3; or a pharmaceutically acceptable salt thereof.  
     
     
       6. A method according to claim  5  wherein the estrogen-dependent cancer is breast or uterine cancer. 
     
     
       7. A method according to claim  6  wherein R 1  and R 2  of said formula I compound each are —OH, R 3  is 1-piperidinyl, and n is 2. 
     
     
       8. A method according to claim  7  wherein said salt thereof is the hydrochloride salt. 
     
     
       9. A method for comprising treating pathological conditions resulting from an estrogen deficiency administering to a woman in need of treatment an effective amount of a compound of formula I                    
       or a pharmaceutically acceptable salt thereof wherein 
       R 1  is —H, —OH, —O(C 1 -C 4  alkyl), —OCOC 6 H 5 , —OCO(C 1 -C 6  alkyl), or —OSO 2 (C 2 -C 6  alkyl);  
       R 2  is —H, —OH, —O(C 1 -C 4  alkyl), —OCOC 6 H 5 , —OCO(C 1 -C 6  alkyl), —OSO 2 (C 2 -C 6  alkyl) or halo;  
       R 3  is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; and  
       n is 2 or 3;  
       in combination with an effective amount of estrogen.